Engineered Protein Inhibitors of SARS-CoV-2 Entry: Difference between revisions
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[[Image:LCB_Method.png|300 px|right|thumb|Figure 3:The use of the De Novo protein design to create the LCB1 and LCB3 inhibitors (7JZL).]] | [[Image:LCB_Method.png|300 px|right|thumb|Figure 3:The use of the De Novo protein design to create the LCB1 and LCB3 inhibitors (7JZL).]] | ||
===The Process of Discovery=== | ===The Process of Discovery=== | ||
The first mini-binder to be created to combat COVID-19 is called <scene name='10/1078124/Ahb2_general/2'>AHB2</scene>. In order to ensure that the mini-binder would bind to the same RBD that the ACE2 was bound to, AHB2 was designed by looking at the specific sequence of ACE2 to find the alpha-helix that makes interactions with the spike receptor binding domain. This design process is referred to as the Rosetta Blueprint protein design. Figure 2 shows the RBD trimer with one part of ACE2 being used for the reference alpha helix to create AHB2 <ref name="Cao">PMID:32907861</ref>. | The first mini-binder to be created to combat COVID-19 is called <scene name='10/1078124/Ahb2_general/2'>AHB2</scene>. In order to ensure that the mini-binder would bind to the same RBD that the ACE2 was bound to, AHB2 was designed by looking at the specific sequence of ACE2 to find the alpha-helix that makes interactions with the spike receptor binding domain. This design process is referred to as the [https://docs.rosettacommons.org/docs/latest/Home Rosetta Blueprint] protein design. Figure 2 shows the RBD trimer with one part of ACE2 being used for the reference alpha helix to create AHB2 <ref name="Cao">PMID:32907861</ref>. | ||
As the AHB2 inhibitors were tested and found to be effective, it was then time to manipulate the mini-binders to create a more effective vaccine. A rotamer interaction field docking method with in silico mini-proteins was used with a scaffold library to generate binders to more distinct regions of the RBD surface <ref name="Cao"/>. This method is known as the de novo protein design and it is how the <scene name='10/1078124/Lcb1_general/2'>LCB1</scene> and <scene name='10/1078124/Lcb3_general/1'>LCB3</scene> mini-binders were created. Figure 3 shows the different LCBs pulled from the scaffold library to create the different LCB inhibitors. | As the AHB2 inhibitors were tested and found to be effective, it was then time to manipulate the mini-binders to create a more effective vaccine. A rotamer interaction field docking method with in silico mini-proteins was used with a scaffold library to generate binders to more distinct regions of the RBD surface <ref name="Cao"/>. This method is known as the de novo protein design and it is how the <scene name='10/1078124/Lcb1_general/2'>LCB1</scene> and <scene name='10/1078124/Lcb3_general/1'>LCB3</scene> mini-binders were created. Figure 3 shows the different LCBs pulled from the scaffold library to create the different LCB inhibitors. | ||
